Summary of work: Comparative anatomic data suggest that an association system of brain regions underwent selective expansion during primate evolution; these regions are selectively vulnerable to Alzheimer's disease. Functional imaging studies using positron emission tomography (PET) show that they become abnormal earlier and more extensively than do other regions. Functional deficits occur at the level of the synapse in these regions. Activation brain blood flow studies with PET were designed to examine synaptic integrity in vivo, and to see how synaptic failure can be reversed by modulatory drugs in affected regions. Affected regions in Alzheimer's disease (AD) demonstrate a reduced critical temperature of membrane lipids, leading to membrane instability and ascribed to reduced concentrations of ethanol plasmalogen.